Improved characterization of quantitative traits and dimensionally distributed complex behaviors during toddlerhood may improve early identification of autism spectrum disorder and related neurodevelopmental disorders. Parents of 205 community-ascertained toddlers (age: mean = 20.2, SD = 2.6 months) completed the Repetitive Behavior Scales for Early Childhood (RBS-EC) and the Video-Referenced Rating of Reciprocal Social Behavior (vrRSB), with longitudinal follow-up of behavioral assessments and/or another round of parent-report questionnaires. Criterion validity was examined both concurrently and longitudinally using the Infant Toddler Social Emotional Assessment (ITSEA) as a criterion anchor. Reciprocal social behavior as measured by the vrRSB was significantly associated with social competence as measured by the ITSEA, longitudinally and concurrently. Reciprocal social behavior was not associated with the externalizing subscale on the ITSEA, providing evidence of discriminant validity. Higher-order repetitive behaviors (restricted interests; rituals and routines) as measured by RBS-EC subscales were associated with the dysregulation and internalizing subscales of the ITSEA, longitudinally and concurrently. All RBS-EC subscales (excepting repetitive motor) were associated concurrently and longitudinally with the dysregulation subscale of the ITSEA. We report evidence of criterion-oriented and discriminant validity for the constructs/domains captured by the RBS-EC and vrRSB. These instruments may be particularly useful in characterizing dimensional variability across the typical-to-atypical continuum.

The current study had three goals. First, we replicated recent evidence that suggests a concurrent relation between attention bias to reward and externalizing and attention problems at age 7. Second, we extended these findings by examining the relations between attention and behavioral measures of early exuberance (3 years), early effortful control (4 years), and concurrent effortful control (7 years), as well as later behavioral problems (9 years). Third, we evaluated the role of attention to reward in the longitudinal pathways between early exuberance and early effortful control to predict externalizing and attention problems. Results revealed that attention bias to reward was associated concurrently and longitudinally with behavioral problems. Moreover, greater reward bias was concurrently associated with lower levels of parent-reported effortful control. Finally, attention bias to reward moderated the longitudinal relations between early risk factors for behavioral problems (gender, exuberance, and effortful control) and later externalizing and attention problems, such that these early risk factors were most predictive of behavioral problems for males with a large attention bias to reward. These findings suggest that attention bias to reward may act as a moderator of early risk, aiding the identification of children at the highest risk for later behavioral problems.

Environmental and biological factors contribute to sleep development during infancy. Parenting plays a particularly important role in modulating infant sleep, potentially via the serotonin system, which is itself involved in regulating infant sleep. We hypothesized that maternal neglect and serotonin system dysregulation would be associated with daytime sleep in infant rhesus monkeys. Subjects were nursery-reared infant rhesus macaques (n = 287). During the first month of life, daytime sleep-wake states were rated bihourly (0800–2100). Infants were considered neglected (n = 16) if before nursery-rearing, their mother repeatedly failed to retrieve them. Serotonin transporter genotype and concentrations of cerebrospinal fluid 5-hydroxyindoleacetic acid (5-HIAA) were used as markers of central serotonin system functioning. t tests showed that neglected infants were observed sleeping less frequently, weighed less, and had higher 5-HIAA than non-neglected nursery-reared infants. Regression revealed that serotonin transporter genotype moderated the relationship between 5-HIAA and daytime sleep: in subjects possessing the Ls genotype, there was a positive correlation between 5-HIAA and daytime sleep, whereas in subjects possessing the LL genotype there was no association. These results highlight the pivotal roles that parents and the serotonin system play in sleep development. Daytime sleep alterations observed in neglected infants may partially derive from serotonin system dysregulation.

The national priority to advance early detection and intervention for children with autism spectrum disorder (ASD) has not reduced the late age of ASD diagnosis in the US over several consecutive Centers for Disease Control and Prevention (CDC) surveillance cohorts, with traditionally under-served populations accessing diagnosis later still. In this review, we explore a potential perceptual barrier to this enterprise which views ASD in terms that are contradicted by current science, and which may have its origins in the current definition of the condition and in its historical associations. To address this perceptual barrier, we propose a re-definition of ASD in early brain development terms, with a view to revisit the world of opportunities afforded by current science to optimize children's outcomes despite the risks that they are born with. This view is presented here to counter outdated notions that potentially devastating disability is determined the moment a child is born, and that these burdens are inevitable, with opportunities for improvement being constrained to only alleviation of symptoms or limited improvements in adaptive skills. The impetus for this piece is the concern that such views of complex neurodevelopmental conditions, such as ASD, can become self-fulfilling science and policy, in ways that are diametrically opposed to what we currently know, and are learning every day, of how genetic risk becomes, or not, instantiated as lifetime disabilities.

This study used repeated measures data to identify developmental profiles of elevated risk for ADHD (i.e., six or more inattentive and/or hyperactive-impulsive symptoms), with an interest in the age at which ADHD risk first emerged. Risk factors that were measured across the first 3 years of life were used to predict profile membership. Participants included 1,173 children who were drawn from the Family Life Project, an ongoing longitudinal study of children's development in low-income, nonmetropolitan communities. Four heuristic profiles of ADHD risk were identified. Approximately two thirds of children never exhibited elevated risk for ADHD. The remaining children were characterized by early childhood onset and persistent risk (5%), early childhood limited risk (10%), and middle childhood onset risk (19%). Pregnancy and delivery complications and harsh-intrusive caregiving behaviors operated as general risk for all ADHD profiles. Parental history of ADHD was uniquely predictive of early onset and persistent ADHD risk, and low primary caregiver education was uniquely predictive of early childhood limited ADHD risk. Results are discussed with respect to how changes to the age of onset criterion for ADHD in DSM5 may affect etiological research and the need for developmental models of ADHD that inform ADHD symptom persistence and desistance.

Early adversities that are caregiving-related (crEAs) are associated with a significantly increased risk for mental health problems. Recent neuroscientific advances have revealed alterations in medial prefrontal cortex (mPFC)-subcortical circuitry following crEAs. While this work has identified alterations in affective operations (e.g., perceiving, reacting, controlling, learning) associated with mPFC–subcortical circuitry, this circuitry has a much broader function extending beyond operations. It plays a primary role in affective meaning making, involving conceptual-level, schematized knowledge to generate predictions about the current environment. This function of mPFC–subcortical circuitry motivates asking whether mPFC–subcortical phenotypes following crEAs support semanticized knowledge content (or the concept-level knowledge) and generate predictive models. I present a hypothesis motivated by research findings across four different lines of work that converge on mPFC–subcortical neuroanatomy, including (a) the neurobiology supporting emotion regulation processes in adulthood, (b) the neurobiology that is activated by caregiving cues during development, (c) the neurobiology that is altered by crEAs, and (d) the neurobiology of semantic-based meaning making. I hypothesize that the affective behaviors following crEAs result in part from affective semantic memory processes supported by mPFC–subcortical circuitry that over the course of development, construct affective schemas that generate meaning making and guide predictions. I use this opportunity to review some of the literature on mPFC–subcortical circuit development following crEAs to illustrate the motivation behind this hypothesis. Long recognized by clinical science and cognitive neuroscience, studying schema-based processes may be particularly helpful for understanding how affective meaning making arises from developmental trajectories of mPFC–subcortical circuitry.

Childhood adversity (CA) increases the risk of subsequent mental health problems. Adolescent social support (from family and/or friends) reduces the risk of mental health problems after CA. However, the mechanisms of this effect remain unclear, and we speculate that they are manifested on neurodevelopmental levels. Therefore, we investigated whether family and/or friendship support at ages 14 and 17 function as intermediate variables for the relationship between CA before age 11 and affective or neural responses to social rejection feedback at age 18. We studied 55 adolescents with normative mental health at age 18 (26 with CA and therefore considered “resilient”), from a longitudinal cohort. Participants underwent a Social Feedback Task in the magnetic resonance imaging scanner. Social rejection feedback activated the dorsal anterior cingulate cortex and the left anterior insula. CA did not predict affective or neural responses to social rejection at age 18. Yet, CA predicted better friendships at age 14 and age 18, when adolescents with and without CA had comparable mood levels. Thus, adolescents with CA and normative mood levels have more adolescent friendship support and seem to have normal mood and neural responses to social rejection.

Relationships with parents and peers are crucial for children's socialization, but how parent–child and peer relationships mutually affect each other is not well understood. Guided by spillover theory, we zoomed in on the bidirectional interplay between parental rejection and warmth on the one hand and peer victimization on the other, and examined whether children's maladjustment symptoms mediated hypothesized cross-domain spillover effects. Data stem from five waves of the longitudinal KiVa study among 9,770 children (50% boys; mean age = 9.16, standard deviation = 1.29). Results from random intercept cross-lagged panel models showed that higher parental rejection and lower parental warmth predicted increases in peer victimization and vice versa across waves, thus supporting the bidirectional model. Moreover, spillover from parent–child rejection and warmth to peer victimization was partially driven by children's depressive symptoms and bullying perpetration. Vice versa, spillover from peer victimization to parent–child rejection and warmth was partially driven by children's social anxiety, depressive symptoms, conduct problems, and bullying perpetration. Thus, children might get caught in persistent problems in two important social domains, and these two domains influence each other through children's maladjustment. Family and school interventions should be integrated to prevent a downwards spiral.

There has been a longstanding debate about the link between callous-unemotional traits and fearlessness. However, biological evidence for a relationship in adolescents is lacking. Using two adolescent samples, we measured emotional reactivity and cardiac measures of sympathetic (pre-ejection period) and parasympathetic (respiratory sinus arrhythmia) reactivity during 3D TV and virtual reality fear induction. Study 1 included 62 community adolescents from a stratified sample. Study 2 included 60 adolescents from Emotional and Behavioral Difficulties schools. Results were consistent across both studies. Adolescents with high callous-unemotional traits showed coactivation of the sympathetic and parasympathetic nervous system. Consistent with these results, youths with callous-unemotional traits self-reported that they felt more in control after the fear induction. Thus, in both samples, youth with callous-unemotional traits displayed a physiological and emotional profile suggesting they maintained control during fear induction. Therefore, it is proposed here that a shift in thinking of youth with callous-unemotional traits as fearless to youth with callous-unemotional traits are better able to manage fearful situations, may be more appropriate.

This study examined relations among parent adverse childhood experiences (ACEs), parent mental distress, child social–emotional functioning, and parent emotional availability (EA) among parents and children served by an Early Head Start program in an American Indian community. The majority of parents and children in the study were American Indian/Alaska Native. American Indian/Alaska Native communities experience relatively high rates of trauma, socioeconomic disparities, and mental health challenges. In this context, young children may be especially vulnerable to early life stress. Further, a strong body of literature demonstrates the long-term effects of ACEs on individuals’ mental health, as well as their child's social–emotional functioning. In this study we examined a model to test the relation of parent ACEs to children's social–emotional functioning, with an indirect effect via a latent “mental distress” variable consisting of parent depression, anxiety, and parenting-related distress. Results supported this model, suggesting that parent ACEs related to children's social–emotional problems by way of parent mental distress. However, when a categorical measure of parent EA was added as a moderator, the model only remained significant in the low EA parent group. These results provided evidence for a “buffering” effect of high parent EA on the relation between parent ACEs, parent mental distress, and children's social–emotional problems.

Studies examining associations between fetal serotonin reuptake inhibitor (SRI) exposure and child autism spectrum disorder (ASD) diagnoses or delayed language remain mixed and rarely prospectively follow children or employ gold-standard assessments. We prospectively followed a cohort of mother–child dyads from pregnancy through early elementary school (N = 178), and obtained maternal and alternate–caregiver ratings of behaviors related to ASD (N = 137), as well as direct, gold-standard assessments of child ASD symptoms and pragmatic language among dyads who experienced prenatal depression and either took SRIs or were medication free during pregnancy (N = 44). Prenatal SRI exposure was related to maternal ratings of ASD-related behaviors (β = 0.24 95% confidence interval; CI [0.07, 0.48]), and, among boys, alternative caregiver ratings (males-only β = 0.28 95% CI [0.02, 0.55], females-only β = −0.21 95% CI [–0.63, 0.08]). However, results of our direct assessments suggest an association between SRI exposure and reduced pragmatic language scores (β = –0.27, 95% CI [–0.53, –0.01], but not ASD (Autism Diagnostic Observation Schedule β = 0.14 95% CI [–0.15, 0.41]; Social Responsiveness Scale β = 0.08 95% CI [–0.25, 0.40]). These discrepancies point to issues regarding how ASD is assessed, and the possibility that SRIs may be more strongly associated with language or other broader behaviors that coincide with ASD. Larger prospective studies that incorporate thorough, gold-standard assessments of ASD, language, and other ASD-related behaviors are needed.

Despite the strong link between childhood maltreatment and psychopathology, the underlying neurodevelopmental mechanisms are poorly understood and difficult to disentangle from heritable and prenatal factors. This study used a translational macaque model of infant maltreatment in which the adverse experience occurs in the first months of life, during intense maturation of amygdala circuits important for stress and emotional regulation. Thus, we examined the developmental impact of maltreatment on amygdala functional connectivity (FC) longitudinally, from infancy through the juvenile period. Using resting state functional magnetic resonance imaging (MRI) we performed amygdala–prefrontal cortex (PFC) region-of-interest and exploratory whole-brain amygdala FC analyses. The latter showed (a) developmental increases in amygdala FC with many regions, likely supporting increased processing of socioemotional-relevant stimuli with age; and (b) maltreatment effects on amygdala coupling with arousal and stress brain regions (locus coeruleus, laterodorsal tegmental area) that emerged with age. Maltreated juveniles showed weaker FC than controls, which was negatively associated with infant hair cortisol concentrations. Findings from the region-of-interest analysis also showed weaker amygdala FC with PFC regions in maltreated animals than controls since infancy, whereas bilateral amygdala FC was stronger in maltreated animals. These effects on amygdala FC development may underlie the poor behavioral outcomes associated with this adverse experience.

Impairment in reciprocal social behavior (RSB), an essential component of early social competence, clinically defines autism spectrum disorder (ASD). However, the behavioral and genetic architecture of RSB in toddlerhood, when ASD first emerges, has not been fully characterized. We analyzed data from a quantitative video-referenced rating of RSB (vrRSB) in two toddler samples: a community-based volunteer research registry (n = 1,563) and an ethnically diverse, longitudinal twin sample ascertained from two state birth registries (n = 714). Variation in RSB was continuously distributed, temporally stable, significantly associated with ASD risk at age 18 months, and only modestly explained by sociodemographic and medical factors (r2 = 9.4%). Five latent RSB factors were identified and corresponded to aspects of social communication or restricted repetitive behaviors, the two core ASD symptom domains. Quantitative genetic analyses indicated substantial heritability for all factors at age 24 months (h2 ≥ .61). Genetic influences strongly overlapped across all factors, with a social motivation factor showing evidence of newly-emerging genetic influences between the ages of 18 and 24 months. RSB constitutes a heritable, trait-like competency whose factorial and genetic structure is generalized across diverse populations, demonstrating its role as an early, enduring dimension of inherited variation in human social behavior. Substantially overlapping RSB domains, measurable when core ASD features arise and consolidate, may serve as markers of specific pathways to autism and anchors to inform determinants of autism's heterogeneity.

Exposure to adverse events is prevalent among youths and robustly associated with risk for depression, particularly during adolescence. The Dimensional Model of Adversity and Psychopathology (DMAP) distinguishes between adverse events that expose youths to deprivation versus threat, positing unique mechanisms of risk (cognitive functioning deficits for deprivation, and altered fear and emotion learning for threat) that may require different approaches to intervention. We examined whether deprivation and threat were distinctly associated with behavioral measures of cognitive processes and autonomic nervous system function in relation to depression symptom severity in a community sample of early adolescents (n = 117; mean age 12.73 years; 54.7% male). Consistent with DMAP, associations between threat and depression symptoms, and between economic deprivation and depression symptoms, were distinctly moderated by physiological and cognitive functions, respectively, at baseline but not follow-up. Under conditions of greater cognitive inhibition, less exposure to deprivation was associated with lower symptom severity. Under conditions of blunted resting-state autonomic response (electrodermal activity and respiratory sinus arrhythmia), greater exposure to threat was associated with higher symptom severity. Our findings support the view that understanding risk for youth depression requires parsing adversity: examining distinct roles played by deprivation and threat, and the associated cognitive and biological processes.

Theories of maladaptive anxiety in children have suggested different developmental trajectories across age. Weems (2008) suggested that one subgroup of children demonstrates high and stable levels of broad anxiety, but shifting levels of dimension-specific symptoms in part due to related normative challenges. In a prospective longitudinal design, the current study examined patterns of dimension-specific anxiety symptoms in subgroups of children following different developmental trajectories of broad anxiety. A total of 300 children (150 girls, 150 boys) ages 8–11 at baseline, completed the Spence Children's Anxiety Scale four times over 3 years. Using latent class growth mixture modeling, we found evidence of three subgroups of children following different trajectories of broad anxiety across age: low-stable, moderate-increasing, and high-decreasing. Compared with other children, the subgroup with moderate and increasing levels of broad anxiety demonstrated an initially higher level of separation anxiety with larger improvement across time but, initially, similar levels of generalized and social anxiety with a larger increase across age. High broad anxiety was partly carried by different sets of dimension-specific symptoms at different ages, which suggests that children with high levels of broad anxiety across time may be more sensitive to normative challenges that happen in typical child development.

Exposure to childhood adversity is a critical risk factor for the development of psychopathology. A growing field of research examines how exposure to childhood adversity is translated into biological risk for psychopathology through alterations in immune system functioning, most notably heightened levels of inflammation biomarkers. Though our knowledge about how childhood adversity can instantiate biological risk for psychopathology is growing, there remain many challenges and gaps in the field to understand how inflammation from childhood adversity contributes to psychopathology. This paper reviews research on the inflammatory outcomes arising from childhood adversity and presents four major challenges that future research must address: (a) the measurement of childhood adversity, (b) the measurement of inflammation, (c) the identification of mediators between childhood adversity and inflammation, and (d) the identification of moderators of inflammatory outcomes following childhood adversity. We discuss synergies and inconsistencies in the literature to summarize the current understanding of the association between childhood adversity, a proinflammatory phenotype, and the biological risk for psychopathology. We discuss the clinical implications of the inflammatory links between childhood adversity and psychopathology, including possibilities for intervention. Finally, this review conclude by delineates future directions for research, including issues of how best to detect, prevent, and understand these “hidden wounds” of childhood adversity.

Understanding differences in social-emotional behavior can help identify atypical development. This study examined the differences in social-emotional development in children at increased risk of an autism spectrum disorder (ASD) diagnosis (infant siblings of children diagnosed with the disorder). Parents completed the Brief Infant-Toddler Social-Emotional Assessment (BITSEA) to determine its ability to flag children with later-diagnosed ASD in a high-risk (HR) sibling population. Parents of HR (n = 311) and low-risk (LR; no family history of ASD; n = 127) children completed the BITSEA when their children were 18 months old and all children underwent a diagnostic assessment for ASD at age 3 years. All six subscales of the BITSEA (Problems, Competence, ASD Problems, ASD Competence, Total ASD Score, and Red Flags) distinguished between those in the HR group who were diagnosed with ASD (n = 84) compared to non-ASD-diagnosed children (both HR-N and LR). One subscale (BITSEA Competence) differentiated between the HR children not diagnosed with ASD and the LR group. The results suggest that tracking early social-emotional development may have implications for all HR children, as they are at increased risk of ASD but also other developmental or mental health conditions.

Although familial adversity is associated with poorer outcomes in childhood and adulthood, little research has looked at the influence of stability or transition between distinct familial adversity subgroups or the impact in adolescence. Using data from the 9-month, 3-, 5-, and 14-year time waves of the Millennium Cohort Study (n > 18,000), we used latent class analysis to identify distinct classes of early familial adversity (marital instability/conflict, “suboptimal” parenting, economic disadvantage, and parental mental health problems) and the impact of these adversity classes on adolescent (a) mental health (including self-harm), (b) risk taking, (c) criminality, and (d) victimization. Four profiles were identified largely differing on economic hardship, family composition, and parental conflict. Across the first three time points, 72% of the sample remained stable, with the remainder transitioning between classes. Adolescents in the higher risk groups (particularly categorized by economic hardship or high parental conflict) had poorer outcomes in adolescence. Transitioning to a higher adversity group at any time in the first 5 years was associated with poorer outcomes but was particularly pronounced when the transition occurred when the child was under 3 years. These findings demonstrate the broad consequences of early familial adversity and the need for targeted early support for at-risk families.